JACC: HEART FAILURE VOL. 7, NO.

8, 2019

ª 2019 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION

PUBLISHED BY ELSEVIER

Hemodynamic Effects of Weight Loss

in Obesity
A Systematic Review and Meta-Analysis

Yogesh N.V. Reddy, MBBS, MSC,a Mahesh Anantha-Narayanan, MBBS,b Masaru Obokata, MD, PHD,a
Katlyn E. Koepp, BSC,a Patricia Erwin, MLS,c Rickey E. Carter, PHD,d Barry A. Borlaug, MDa

ABSTRACT

OBJECTIVES The authors aimed to explore whether weight loss may improve central hemodynamics in obesity.

BACKGROUND Hemodynamic abnormalities in obese heart failure with preserved ejection fraction patients are
correlated with the amount of excess body mass, suggesting a possible causal relationship.

METHODS Relevant databases were systematically searched from inception to May 2018, without language restriction.
Studies reporting invasive hemodynamic measures before and following therapeutic weight loss interventions in
patients with obesity but no clinically overt heart failure were extracted.

RESULTS A total of 9 studies were identified, providing data for 110 patients. Six studies tested dietary intervention and
3 studies tested bariatric surgery. Over a median duration of 9.7 months (range 0.75 to 23.0 months), a median weight
loss of 43 kg (range 10 to 58 kg) was associated with significant reductions in heart rate (
9 beats/min, 95% confidence
interval [CI]:
12 to
6; p < 0.001), mean arterial pressure (
7 mm Hg, 95% CI:
11 to
3; p < 0.001), and resting
oxygen consumption (
85 ml/min, 95% CI:
111 to
60; p < 0.001). Central cardiac hemodynamics improved,
manifested by reductions in pulmonary capillary wedge pressure (
3 mm Hg, 95% CI:
5 to
1; p < 0.001) and mean
pulmonary artery pressure (
5 mm Hg, 95% CI:
8 to
2; p ¼ 0.001). Exercise hemodynamics were assessed in a subset
of patients (n ¼ 49) in which there was significant reduction in exercise pulmonary artery pressure (p ¼ 0.02).

CONCLUSIONS Therapeutic weight loss in obese patients without HF is associated with favorable hemodynamic
effects. Randomized controlled trials evaluating strategies for weight loss in obese patients with heart failure such as the
obese phenotype of heart failure with preserved ejection fraction are needed. (J Am Coll Cardiol HF 2019;7:678–87)
© 2019 by the American College of Cardiology Foundation.

O besity is a major risk factor for develop-

ment of heart failure (HF), and in partic-
ular, HF with preserved ejection fraction
(HFpEF) (1–5). Among patients with unexplained dys-
pnea, the mere presence of obesity increases the odds
that HFpEF is the cause of symptoms by more than 3-
fold (3). Compared with nonobese HFpEF patients,
those with obesity present with more severe HF
symptoms, adverse hemodynamics, greater systemic
inflammation, and impaired exercise capacity (6–8).
Abnormal hemodynamics play a central role in the
pathophysiology of HFpEF, directly contributing to
symptoms of dyspnea, worsening functional capacity,
and increasing morbidity and mortality (9–11). Among
patients with obesity and HFpEF, the magnitude of
elevation in filling pressures is directly related to the
amount of excess body mass, suggesting a possible
causal relationship (6). Modest, therapeutic weight
loss induced by caloric restriction in patients with
obesity and HFpEF improves aerobic capacity (12),

From the aDepartment of Cardiovascular Medicine, University of Minnesota, Minneapolis, Minnesota; bDivision of Cardiovascular
c
Diseases, University of Minnesota, Minneapolis, Minnesota; Department of Medical Education, Mayo Clinic, Rochester,
Minnesota; and the dHealth Sciences Research, Mayo Clinic, Rochester, Minnesota. Dr. Borlaug is supported by National Institutes
of Health grants R01 HL128526, R01 HL 126638, U01 HL125205, and U10 HL110262. All other authors have reported that they have
no relationships relevant to the contents of this paper to disclose.

Manuscript received February 16, 2019; revised manuscript received April 25, 2019, accepted April 25, 2019.

ISSN 2213-1779/$36.00 https://doi.org/10.1016/j.jchf.2019.04.019

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JACC: HEART FAILURE VOL. 7, NO. 8, 2019
AUGUST 2019:678–87
but its effects on directly measured invasive cardiac
hemodynamics have not been examined.
To explore whether therapeutic, purposeful weight
loss might be a viable treatment for obese patients
with HF, we conducted a systematic review and meta-
analysis of prior studies reporting the effects of
weight loss on central hemodynamics assessed inva-
sively in patients with obesity but without frank HF.
SEE PAGE 688
METHODS
STUDY AND PATIENT SELECTION. Randomized and
observational studies evaluating the effects of weight
loss on invasive hemodynamic measurements before
and following weight loss in obese adults (age > 18
years) were identified up to May 1, 2018. (The detailed
search strategy is included in the Online Appendix.)
Studies were required to report pre- and post-weight
loss invasive hemodynamics as mean and SD,
such that mean differences could be calculated for
each variable. Studies were included regardless of
method of weight loss (caloric restriction or bariatric
surgery). All abstracts were screened by a single
investigator (Y.N.R.) to form the list for full-text re-
view. Full-text reviews were performed by Y.N.R. and
M.A.N. in duplicate. Any discrepancy between the
2 reviewers was resolved by consulting the third
reviewer (B.A.B.).
DATA ANALYSIS. The mean  SD of
hemodynamic variables of interest were extracted
from each study before and after weight loss to
calculate mean differences. In the subset of studies
that also evaluated exercise hemodynamics before
and after weight loss, mean differences between peak
exercise hemodynamics were also compared before
and after weight loss. Individual patient data were
available from tables in some studies and were used
to summarize statistics when not directly reported in
the original publication.
For studies that did not report the necessary raw
data for calculation, this was calculated
included bar graphs and figures when available after
creating a digitized curve using Engauge digitizer 4.1
(13). Detailed baseline characteristics for age, sex,
body mass index, weight before and after weight loss,
and duration of follow-up were also extracted. A
random effects model was used to summarize dif-
ferences following weight loss among subjects who
underwent therapeutic weight loss intervention. Risk
of bias was assessed by 1 reviewer independent from
study selection (M.O.) using the New Castle Ottawa
Scale for cohort studies (Online Appendix).
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Reddy et al. 679
Weight Loss on Central Hemodynamics in Obesity
STATISTICAL ANALYSIS. Data were pooled ABBREVIATIONS
in a random effects model with the pooled AND ACRONYMS
effect size represented as mean difference
HFpEF = heart failure with
after weight loss, with 95% confidence inter- preserved ejection fraction
val (CI) limits. For ease of reporting, differ-
VO2 = oxygen consumption
ences were calculated as post-minus pre-
weight loss values, such that a negative difference in
means indicates a reduction in value after weight loss.
Baseline hemodynamics were summarized across
studies as weighted means and Cochrane’s Q-statistics
were used to determine the heterogeneity of included
studies for each outcome. Heterogeneity was calcu-
lated using prediction intervals as recommended by
Borenstein et al. (14). I 2 values of <25%, 25% to 50%,
and 50% to 75% were considered as low, moderate,
and high heterogeneity, respectively. A p value <0.05
was considered statistically significant. Analyses were
performed by M.A.N. and Y.N.R. using the software
Comprehensive Meta-analysis (version 3.3).
RESULTS
STUDY SELECTION. On the initial library search, 1,911
studies were identified for abstract screening
(Figure 1, Online Appendix). After manual review of
all abstracts, 25 studies were selected for full-text
review and were evaluated by 2 authors, who inde-
pendently identified the same 9 studies for inclusion.
No studies including patients with overt obesity-
related HF were identified that reported pre- and
central post-weight loss hemodynamics. Among 200
randomly evaluated abstracts, no disagreements on
exclusion were noted between the 2 reviewing au-
thors. Data were extracted by Y.N.R. from individual
studies and then verified in duplicate by M.A.N.
Three of the studies (15–17) required some summary
data extraction from bar graphs when not included in
the text or tables.
Fifteen studies did not include the necessary
invasive assessment of central hemodynamics before
and after weight loss and were therefore excluded
(Figure 1). One study by Andersson (18) included
from duplicate patients with another study by the same
authors (19) and was therefore excluded. The included
Andersson study contained 1 arm of patients treated
with both weight loss and salt loading; the data from
those subjects were therefore not included (19).
Of the 9 studies identified, no randomized trials
were identified. All were prospective observational
studies reporting invasive hemodynamic, metabolic,
and neurohormonal changes following therapeutic
weight loss interventions (15–17,19–24) (Table 1).
STUDY CHARACTERISTICS. The studies included
represent data from a total of 110 patients with
680 Reddy et al. JACC: HEART FAILURE VOL. 7, NO. 8, 2019

Weight Loss on Central Hemodynamics in Obesity AUGUST 2019:678–87

F I G U R E 1 Identification of Studies

Screening strategy resulting in 1,911 abstracts screened for 9 eligible studies.

obesity. Six studies evaluated effects following
caloric restriction (diet intervention) and 3 studies
evaluated changes following bariatric
(Table 1). The median of study level mean age was 37
years (range 32 to 43 years), with baseline weight of
124 kg (range 96 to 166 kg) and included mostly
women (median 81% [range 50% to 87%]). Hemody-
namic evaluation was performed at baseline before
intervention and following weight loss at a median
follow-up of 9.7 months (range 0.75 to 23 months).
The magnitude of weight loss achieved across studies
was 43 kg (range 10 to 58 kg), which represented an
approximate 25% weight loss (range 9% to 42%).
BASELINE OXYGEN DELIVERY, METABOLISM, AND
HEMODYNAMICS. The weighted mean heart rate and
mean arterial pressures before weight loss were 76
beats/min (range 63 to 82 beats/min) and 104 mm Hg
(range 94 to 114 mm Hg), respectively (Table 2).
Resting oxygen consumption (VO 2) before weight loss
was 362 ml/min (range 360 to 381 ml/min), w50%
higher than published normative values in non-obese
adults (241  57 ml/min) (25), in keeping with the
increased metabolic rate associated with excess
body mass. Plasma volume was 6.1 l/min (range 4.9 to
surgery 7.8 l/min), coupled with a borderline increase in
resting cardiac output at 6.4 l/min (range 5.7 to
7.6 l/min). There were also borderline elevations in
left-sided cardiac filling pressures (pulmonary capil-
lary wedge pressures [PCWP]: 12 mm Hg, range 10 to
17 mm Hg) and mean pulmonary artery pressures
(23 mm Hg; range 19 to 36) (Table 2).
EFFECTS OF WEIGHT LOSS ON OXYGEN DELIVERY
AND METABOLISM. Following weight loss, there was
a 24% reduction in resting VO 2 (
85 ml/min, 95% CI:

111 to
60; p < 0.001; Figure 2, Central Illustration).
This was coupled with a 9% decrease in cardiac output
(
0.64 l/min, 95% CI:
0.79 to
0.50; p < 0.001;
Table 2, Online Figures 1 to 3). Resting arterial venous
oxygen (O 2) difference decreased, indicating less
O 2 extraction in the tissues (
0.43 ml/dl, 95% CI:

0.85 to
0.01; p ¼ 0.04), even as cardiac output
decreased. There was an 11% reduction in heart rate
(
9 beats/min, 95% CI:
12 to
6; p < 0.001), with no
change in stroke volume (
1 ml, 95% CI:
9 to þ6;

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T A B L E 1 Study Details and Patient Demographics

Body Weight
Sample Follow-Up, Hemodynamic and
First Author, Year (Ref. #) Size Age, yrs Female, % Intervention Pre, kg Post, kg Months Metabolic Variables Assessed

Alaud-din A et al., 1990 (20) 12 NA 87 BS 132  17 77  5 13  4 CO, SV, HR

Alexander and Peterson, 1972 (21) 9 38  13 78 CR 166  31 111  28 13 (4-34) PCWP, PAm, MAP, CO, SV, HR, SVR,
BV, VO2, AVO2D
Andersson et al., 1984 (19) 10 51  4 NA CR 98  8 89  9 NA MAP, CO, SV, HR, SVR, BV
Backman et al., 1979 (22) 22 35  2 77 BS 146  4 88  3 23 (10-38) PCWP, PAm, PASP, MAP, CO, SV,
HR, VO2, AVO2D
Kaltman and Goldring, 4 32  9 50 CR 155  33 116  17 4-20 PCWP, RAP, MAP, CO, SV, HR, VO2, AVO2D,
1975 (23)
Reisin et al., 1983 (24) 12 NA NA CR 96  4 86  4 93 MAP, CO, SV, HR, SVR
Slany et al., 1974 (15) 12 43  13 58 CR 115  18 104  17 0.5-1 PCWP, PAm, MAP, CO, HR,
Slany et al., 1975 (16) 11 38  9 79 CR 116  15 NA* 0.5-0.7 PCWP, PAm, RAP, MAP, CO, SV, HR
Sugerman et al., 1988 (17) 18 NA NA BS 224  59 (% IBW) 167  57 (% IBW) 3-9 PCWP, PAm

Values are n, mean  SD, or median (interquartile range). *Although absolute body weight post-intervention was not reported in the Slany et al. (1975) study, the range of weight loss was 8 to 15 kg.
AVO2D ¼ arterial-venous oxygen content difference; BV ¼ blood volume; BS ¼ bariatric surgery; BV ¼ blood volume; CO ¼ cardiac output; CR ¼ caloric restriction; HR ¼ heart rate; IBW ¼ ideal body
weight; MAP ¼ mean arterial pressure; NA ¼ data not available; PAm ¼ mean pulmonary artery pressure; PASP ¼ pulmonary artery systolic pressure; RAP ¼ right atrial pressure; SV ¼ stroke volume;
SVR ¼ systemic vascular resistance; VO2 ¼ oxygen consumption.

p ¼ 0.70). Heterogeneity was high for changes in heart in the same 2 studies of borderline significance
rate (I 2 ¼ 57%; p ¼ 0.022) (Table 2). There was a trend (
0.08 ng/ml/h, 95% CI:
0.16 to
0.001; p ¼ 0.04).
toward a reduction in blood volume following weight EFFECTS OF WEIGHT LOSS ON EXERCISE
loss (
0.44 l; 95% CI:
1.05 to 0.17; p ¼ 0.16) (Table 2). HEMODYNAMICS. Five studies reported invasive
Weight loss was associated with a 7% reduction in hemodynamics at peak exercise before and after
mean arterial pressure (
7 mm Hg, 95% CI:
11 to
3; weight loss, or included necessary raw data to
p < 0.001) (Table 2). calculate means and SDs using data from a subset
EFFECTS OF WEIGHT LOSS ON HEMODYNAMICS. of 49 patients (Table 2, Online Figures 8 to 13). The
Weight loss was associated with significant improve-
ments in biventricular filling pressures, with a 26% T A B L E 2 Estimates of Hemodynamic and Metabolic Parameters Before and After
reduction in PCWP (
3 mm Hg, 95% CI:
5 to
1; Weight Loss

p < 0.001) (Figure 3) and 46% reduction in mean right

Weighted
atrial pressure (
2 mm Hg, 95% CI:
5 to
0.1; Number of Mean, Mean Difference
Studies Pre WL Following WL 95% CI p Value I2 , %
p ¼ 0.042). Heterogeneity was high for the changes in
Rest
right atrial pressure (Table 2, Online Figures 4 to 7).
Heart rate, min
1 8 (93) 76
9
11.7 to
5.7 <0.001 57*
Concordant with the reduction in left-sided filling
Mean arterial 7 (81) 104
7
11.3 to
3.3 <0.001 41
pressures, mean pulmonary artery pressures were pressure, mm Hg
also reduced by 22% following weight loss Oxygen consumption, 3 (35) 362
85
111 to
60 <0.001 0
ml/min
(
5 mm Hg, 95% CI:
8 to
2; p ¼ 0.001) (Figure 4).
Right atrial pressure, 3 (27) 5
2.4
4.8 to
0.1 0.04 81*
EFFECTS OF WEIGHT LOSS ON GAS EXCHANGE AND mm Hg

NEUROHORMONES. One study of patients with Mean pulmonary artery 4 (60) 23
5.2
8.1 to
2.2 0.001 45
pressure, mm Hg
obesity-hypoventilation syndrome reported changes
Pulmonary wedge 6 (76) 12
3.2
5.0 to
1.4 <0.001 40
in the partial pressure of arterial carbon dioxide in 18 pressure, mm Hg
patients, and there was a significant reduction with Cardiac output, l/min 8 (93) 6.4
0.6
0.8 to
0.5 <0.001 0

weight loss from 52  7 to 42  4 mm Hg (p < 0.0001) Arterial-venous O2 3 (35) 4.6
0.4
0.9 to
0.01 0.04 0
difference, ml/ml
(17). This change was coupled with an increase in
Exercise
partial pressure of arterial O2 from 50  10 to 69  Heart rate, min
1 5 (61) 119
4
7.8 to 0.2 0.07 23
14 mm Hg (p < 0.0001). Two studies reported plasma Mean arterial pressure, 4 (49) 124
13
21.6 to
5.2 0.001 26
norepinephrine levels and plasma renin activity mm Hg
Oxygen consumption, 3 (35) 1,237
231
361 to
100 <0.001 0
(19,22). Point estimates suggested reduction in
ml/min
norepinephrine that was not statistically significant
(
205, 95% CI:
451.31 to 40.63; p ¼ 0.10), but Values are n or n (%), unless otherwise indicated. The p value reflects the change with weight loss.
*Heterogeneity p value < 0.05.
heterogeneity was high (I 2 ¼ 98%; p < 0.0001) (16,21). I2 ¼ reflects the heterogeneity for the change in each parameter with weight loss; WL ¼ weight loss.
There was a small reduction in plasma renin activity

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682 Reddy et al. JACC: HEART FAILURE VOL. 7, NO. 8, 2019

Weight Loss on Central Hemodynamics in Obesity AUGUST 2019:678–87

F I G U R E 2 Change in Resting Oxygen Consumption With Weight Loss

Forest plot showing reduction in resting oxygen consumption (VO2) with weight loss. LL ¼ lower limit; UL ¼ upper limit.

weighted mean of peak exercise wedge pressure was
22 mm Hg (range 20 to 34 mm Hg) and pulmonary
artery mean pressure was 33 mm Hg (range 28 to
37 mm Hg). Following weight loss, there was a
reduction in peak pulmonary artery mean pressure
(
5 mm Hg, 95% CI:
8 to
1; p ¼ 0.02) and mean
arterial pressure (
13 mm Hg, 95% CI:
22 to
5; p ¼
0.001). There was a trend to lower PCWP with ex-
ercise (
3 mm Hg, 95% CI:
6 to 1; p ¼ 0.19).
Consistent with the reduction in resting VO 2, there
was similar reduction in peak exercise
(
230 ml/min, 95% CI:
361 to
100; p < 0.001)
(Table 2, Online Figures 14 and 15), which was related
to reductions in both exercise cardiac
(
1.45 l/min, 95% CI:
2.60 to
0.31; p ¼ 0.01), and
arterial-venous O 2 content difference (
0.78 ml/dl,
95% CI:
1.35 to
0.21; p ¼ 0.008). Peak ergometric
workloads achieved during exercise were not reported
in the studies.
STUDY QUALITY AND RISK OF BIAS. Quality assess-
ment was performed using a modified New Castle
Ottawa Scale for cohort studies. Included studies
demonstrated high quality with low risk of bias
(Online Table 1). One of the included studies (19)
evaluated the effects of weight loss
through both caloric and sodium restriction, but
exclusion of this study in a sensitivity analysis did
not alter the results (Online Table 1).
DISCUSSION
This systematic review and meta-analysis summarizes
the existing evidence regarding the effects of thera-
peutic weight loss on invasive hemodynamics in pa-
tients with obesity, but no clinical HF. We observed
VO 2 that weight loss is associated with significant re-
ductions in biventricular filling pressures and pulmo-
nary artery pressure, heart rate, cardiac output,
output systemic blood pressure, and whole-body oxygen
consumption (Central Illustration). In a smaller sub-
analysis, there were improvements or trends to
improvement in exercise hemodynamics with weight
loss. These data, derived exclusively from observa-
tional cohort studies, raise the possibility that thera-
peutic weight loss interventions may be effective to
mitigate the hemodynamic derangements that
contribute to morbidity and mortality in people with
the obese phenotype of HFpEF, and potentially
even obese patients with HF with reduced ejection
achieved fraction.

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AUGUST 2019:678–87 Weight Loss on Central Hemodynamics in Obesity

C ENTR AL I LL U STRA T I O N Changes in Central Hemodynamics and Metabolism Following Weight Loss

*
–10
*
*
% Change with Weight Loss

–20

* *
*
–30

–40

–50 *
Whole-Body Heart Cardiac Mean Stroke Right Pulmonary Pulmonary
Oxygen Rate Output Arterial Volume Atrial Wedge Artery
Consumption Pressure Pressure Pressure Pressure
Reddy, Y.N.V. et al. J Am Coll Cardiol HF. 2019;7(8):678–87.

Mean percent changes in resting metabolism, vital signs, and hemodynamics. *p < 0.05.

OBESITY AND ITS EFFECT
HEMODYNAMICS. Obesity has become 1 of the most
important causes of HF in the modern era, particu-
larly HFpEF (1–8). Abnormal hemodynamics play a
central role in the pathophysiology of HFpEF (9–11).
In HFpEF patients with obesity, the magnitude of
PCWP elevation is directly related to the amount of
excess body mass (6). In contrast, this relationship is
absent among nonobese HFpEF patients. This sug-
gests that excess adipose may be an important pro-
moter of adverse hemodynamics in the obese
phenotype of HFpEF. If this is true, then weight
loss would be expected to improve these hemody-
namic derangements.
Consistent with this hypothesis, we observed sig-
nificant improvements in cardiac filling pressures and
pulmonary artery pressures in patients with obesity
but no clinical diagnosis of HF. These data support,
but do not prove, a causative role for excess adiposity
in the pathogenesis of elevated filling pressures and
pulmonary pressures in obesity, even as hemody-
namic findings at baseline (before weight loss) were
only borderline abnormal.
ON CENTRAL POTENTIAL MECHANISMS OF BENEFIT. The consis-
tent improvement in biventricular filling pressures,
lowering of cardiac output and blood pressure
collectively suggest that relief of volume overload
from weight loss may have been a contributor to the
improvements in PCWP. Although the point estimates
of blood volume reduction with weight loss were not
statistically significant, only 3 of the included studies
directly measured blood volume, which may have
compromised power. The observed reductions in
systemic blood pressure and cardiac output would be
expected to ameliorate the excessive ventricular
workload in obesity, and metabolic improvements
associated with weight loss may improve myocardial
substrate use and efficiency (26).
The favorable hemodynamic effects observed in
the current study are consistent with salutary effects
noted in prior noninvasive echocardiographic
studies, in which reductions in ventricular mass with
weight loss have variably been associated with im-
provements in myocardial function (27–29). Nonin-
vasive estimates of hemodynamics are imprecise,
however, particularly among obese patients where

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Weight Loss on Central Hemodynamics in Obesity AUGUST 2019:678–87

F I G U R E 3 Change in Resting Pulmonary Capillary Wedge Pressure With Weight Loss

Forest plot showing reduction in resting pulmonary capillary wedge pressure (PCWP) with weight loss. Abbreviations as in Figure 2.

image quality may be compromised. For this reason,
we restricted the analysis to studies in which invasive
central hemodynamics were measured directly rather
than using noninvasive surrogates.
The reduction in cardiac output following weight
loss was driven by a decrease in heart rate rather than
stroke volume. This suggests a reduction in sympa-
thetic tone, which is often elevated in obesity, and is
consistent with the trend to reductions in plasma
norepinephrine and renin activity in the 2 studies
that reported these measures (19,22). The potential
neurohormonal basis for obesity-related HFpEF rep-
resents an area of intense interest, but remains poorly
understood (30).
At first glance, one might consider a reduction in
cardiac output and VO2 (an indicator of fitness) to
imply a detrimental effect of weight loss; however, it
must be remembered that cardiac output increases
relative to metabolic demand (31). Excessive in-
creases in VO 2, as are observed in obesity, may be
detrimental or even lead to high output HF (32). The
excess body mass in obesity increases the metabolic
work (VO2 ) required for locomotion, decreasing effi-
ciency (6,8).
Even as cardiac output at rest and with exercise
was reduced, we observed that weight loss in obese
patients reduced the arterial-venous oxygen content
difference, both at rest and at peak exercise. This
suggests more favorable O 2 delivery relative to
metabolic demand because venous O 2 content is
greater despite lower total cardiac output. Viewed in
this light, the tandem reductions in VO 2, cardiac
output, and arterial-venous oxygen content differ-
ence together suggest improved total efficiency and
net oxygen delivery to exercising muscle following
weight loss.
POTENTIAL FOR WEIGHT LOSS TO TREAT HF. Weight
loss in obese patients without HF mitigates age-
related ventricular stiffening (33) and decreases inci-
dence of new-onset HF, yet the mechanisms remain
unclear (34,35). Only 1 clinical trial has been pub-
lished to date examining the effects of weight loss
intervention as a treatment for HFpEF. In an elegant
trial, Kitzman and colleagues (12) demonstrated that
weight loss achieved through caloric restriction (400
kcal/day), or the combination of caloric restriction
and exercise training, improved aerobic capacity and

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AUGUST 2019:678–87 Weight Loss on Central Hemodynamics in Obesity

F I G U R E 4 Change In Resting Pulmonary Artery Pressure With Weight Loss

Forest plot showing effect of weight loss on resting mean pulmonary artery (PA) pressure. Abbreviations as in Figure 2.

quality of life assessed by the Kansas City Cardio-
myopathy Questionnaire. Kitzman and colleagues did
not measure direct hemodynamic effects of weight
loss, but it is notable that the amount of weight loss
achieved >20 weeks with caloric restriction (mean

7 kg) was substantially lower than that observed
in this review (
43 kg), which included patients
that underwent bariatric surgery, which produces
greater magnitude of weight loss as well as more
profound secondary benefits on insulin sensitivity,
inflammation, lipids, and mechanical complications
of obesity (34,35). The studies included in this
review tested weight loss alone and not the combi-
nation of weight loss and increases in physical
activity, as is currently recommended. Isolated
weight loss without concomitant resistance and aer-
obic exercise training may result in loss of lean mass,
which could prove harmful in older patients with
HFpEF. Considering the current data with the study
from Kitzman and colleagues, it is clear that ran-
domized trials testing more aggressive weight loss
interventions, together with appropriate lifestyle
and physical activity interventions are necessary in
HFpEF, as well as HF with reduced ejection fraction,
where favorable effects on hemodynamics might also
be effective.
STUDY LIMITATIONS. Because the studies were per-
formed at different centers and across different eras,
hemodynamic evaluations were not standardized,
which in addition to the modest sample size across
studies, may contribute to wider variability and
greater heterogeneity. This limitation would only
have been expected to bias the results toward the
null, however. Given the need for repeat invasive
assessments, the number of subjects for whom data is
available was modest and follow-up assessments
were not uniformly performed, which may limit the
ability to properly estimate the benefits of weight loss
on hemodynamics. Individual-level patient data were
not available in the majority of studies precluding
attempts at patient-level meta-analyses, and baseline
characteristics such as age, sex, and magnitude of
weight loss were not uniformly reported. Most of the
included studies are 20 to 40 years old, and we did
not identify any more contemporary studies in our

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686 Reddy et al.
Weight Loss on Central Hemodynamics in Obesity
search. This likely relates to the greater use of echo-
cardiography in the current era, particularly for
repeat assessments, which was not available when
most of these studies were reported. Although this
limitation may affect the applicability of these data to
the current era, it seems unlikely that the hemody-
namic effects of weight loss in humans would be
likely to differ in a meaningful way across eras. There
were no randomized trials identified in our system-
atic review; accordingly, there is no control group for
comparison, making it difficult to determine whether
observed hemodynamic changes
related to weight loss. This observation emphasizes
the need for well-performed prospective randomized
trials, testing the hypothesis that weight loss might
improve hemodynamics and other clinical endpoints
in obese patients with HF. The weight loss in-
terventions administered were not uniform across
study groups and thus we cannot comment on the
specific efficacy of particular interventions of weight
loss to improve central hemodynamics. The studies
also did not provide sufficient data to understand if
the maximum weight loss had been observed at the
post-intervention measurement period, and there
was variability in the time of follow-up, which may
also confound interpretation. Gas exchange data were
only available from 1 study evaluating weight loss in
patients with obesity hypoventilation syndrome, and
it is not clear whether similar changes would be
observed in other obese populations or whether
favorable effects on gas exchange might be related to
hemodynamic changes following weight loss. The
number of studies does not provide adequate power
to evaluate for potential dose-response relationships
between weight loss and hemodynamic benefits. The
mean age of patients included in these studies is
much lower than typical HFpEF patients, and it is
unclear how age and disease state may modify the
hemodynamic response to aggressive weight loss.
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JACC: HEART FAILURE VOL. 7, NO. 8, 2019
AUGUST 2019:678–87
CONCLUSIONS
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KEY WORDS heart failure, invasive
hemodynamics, meta-analysis, obesity,
weight loss
A PP END IX For supplemental materials,
figures, and tables, please see the online
version of this paper.